The adhesion of Streptococcus sanguis to a tooth is seminal in the formation of dental plaque. To understand the selective advantage of S. sanguis in this niche, adhesion is typically modelled by mixing bacterial cells with saliva-coated hydroxyapatite (sHA) in physiological buffer. Data from this model suggest that protein "adhesins" of certain strains bind S. sanguis to sHA by high affinity, chemically-specific interactions. Cooperative high avidity, weak intermolecular forces then stabilize adhesion. This project will characterize the molecular basis of specificity exhibited in the interactions attributable to an 87 kDa S. sanguis "adhesin" and its binding site(s) on sHA. Specialized probes will be developed from polyclonal and monoclonal reagents reactive with S. sanguis to show antigenic determinants and epitopes of interest. Stereochemically complimentary sHA binding sites will be identified with antibodies specific for the antigen combining sites of the anti-S. sanguis antibody reagents. These anti-idiotype monoclonal antibodies will mimic the S. sanguis epitope and bind to the same, complimentary sHA epitopes. These binding site epitopes on sHA receptors will be isolated using the anti-idiotype antibodies. S. sanguis and salivary epitopes will be characterized. Amino acid sequencing will allow synthesis of peptide analogues of minimal epitopes which will be prepared as synthetic antigens for new antibody probes and also used as competitive haptens in binding assays. Comparative antibody binding, amino acid sequencing, and NMR of epitopes will demonstrate the contribution of primary sequence and conformation to specificity. These studies will advance our understanding of molecular mechanisms of oral ecology with a long term goal of modulating the environment to promote health.